4-Dimethylaminopyridinium chlorochromate as an oxidizing agent for conversion of alcohols to their respective ketones

ABSTRACT

The novel compound 4-dimethylaminopyridinium chlorochromate has been found to be an effective oxidizing agent for converting alcohols to their respective aldehydes or ketones, especially for the selective conversion of allylic and benzylic alcohols to their corresponding aldehydes and ketones.

This application is a division of application Ser. No. 406,585, filedAug. 9, 1982 now U.S. Pat. No. 4,438,269.

BACKGROUND OF THE INVENTION

Chromium (VI) reagents have been widely used in organic chemistry forthe oxidation of primary and secondary alcohols to carbonyl compounds.Pyridine-chromium trioxide complexes, pyridinium chlorochromate andbipyridine-chromium trioxide complexes have been especially usefulreagents for the mild oxidation of primary alcohols to aldehydes. Thereare, however, some significant difficulties associated with thesereagents. For instance, chromium containing by-products oftencontaminate the desired products, requiring time-consumingpurifications. Also, polymeric chromium containing tars may be formedwhich contaminate both the reaction and work-up apparatus. In addition,to date, little useful selectivity has been observed in the oxidation ofpolyhydroxy compounds using chromium (VI) oxidizing reagents.

SUMMARY OF THE INVENTION

A novel compound, 4-dimethylaminopyridinium chlorochromate, has beendiscovered which is useful as an oxidizing agent. The compound isespecially useful as an oxidizing agent for the conversion of alcoholsto their corresponding carbonyl compounds. Furthermore, the compound isa particularly useful oxidizing agent in that it will selectivelyoxidize allylic and/or benzylic alohols to their corresponding carbonylswhile leaving other alcohol groups which may be present during theoxidation reaction substantially intact. The compound is also useful forselectively oxidizing polyhydroxy compounds when it is desired that onlycertain selected hydroxyl groups be converted to carbonyls. Thus, forexample, steroid compounds containing both hindered secondary hydroxylsand non-hindered secondary hydroxyls may be oxidized with DMAP.HCrO₃ Clto convert the hindered secondary hydroxyl group to a ketone, whileleaving the non-hindered secondary hydroxyl group substantially intact.

Thus, in accordance with this invention there is provided the compound4-dimethylaminopyridinium chlorochromate.

In accordance with this invention there is also provided a process foroxidizing an alcohol to a corresponding carbonyl compound by reactingthe alcohol and 4-dimethylaminopyridinium chlorochromate.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

THe compound of this invention, 4-dimethylaminopyridiniumchlorochromate, has the following structure: ##STR1## and, forconvenience, will sometimes be referred to herein as DMAP.HCrO₃ Cl.

DMAP.HCrO₃ Cl may be readily prepared by adding 4-dimethylaminopyridineto a vigorously stirred cold solution of CrO₃ in hydrochloric acid. Theresulting product is a yellow-orange crystalline solid which isnon-hygrosopic and shelf-stable.

DMAP.HCrO₃ Cl is useful as an oxidizing agent, especially for theselective conversion of alcohols to their corresponding carbonylcompounds. Thus, in the practice of the process of this invention, analcohol may be converted to the corresponding carbonyl compound byreacting the alcohol with about 4-6 fold excess of DMAP.HCrO₃ Cl in asuitable solvent such as, for example, dichloromethane. The particularreaction conditions, i.e. reaction temperature, reaction time and thelike, will, of course, vary depending upon the particular alcoholemployed. The resulting product contains the desired carbonyl compoundand a brown chromium by-product which can be completely removed byfiltration with, for example, Celite® filter aid. Typically, no4-dimethylaminopyridine is observed in the crude filtrate. Standardrecovery techniques may be employed, such as, for example, directKugelrohr distillation for sensitive products, or washing with 2Nhydrochloric acid, followed by dilute sodium carbonate wash, drying anddistillation or crystallization.

The process of this invention may be illustrated by, but is not intendedto be limited to, the following reactions:

    __________________________________________________________________________                        Conditions Product                                        Alcohol             Equivalents, Time                                                                        Typical % Yield                                __________________________________________________________________________    Oxidation of Benzylic Alcohols to Aldehydes                                   Using DMAP.HCrO.sub.3 Cl                                                       ##STR2##                                                                                          ##STR3##                                                                                 ##STR4##                                                                     64%                                             ##STR5##                                                                                          ##STR6##                                                                                 ##STR7##                                                                     73%                                             ##STR8##                                                                                          ##STR9##                                                                                 ##STR10##                                                                    78%                                             ##STR11##                                                                                         ##STR12##                                                                                ##STR13##                                                                    87%                                             ##STR14##                                                                                         ##STR15##                                                                                ##STR16##                                                                    98%                                             ##STR17##                                                                                         ##STR18##                                                                                ##STR19##                                                                    43%                                             ##STR20##                                                                                         ##STR21##                                                                                ##STR22##                                                                    91%                                             ##STR23##                                                                                         ##STR24##                                                                                ##STR25##                                                                    91%                                             ##STR26##                                                                                         ##STR27##                                                                                ##STR28##                                                                    86%                                             ##STR29##                                                                                         ##STR30##                                                                                ##STR31##                                                                    88%                                             ##STR32##                                                                                         ##STR33##                                                                                ##STR34##                                                                    72%                                             ##STR35##                                                                                         ##STR36##                                                                                ##STR37##                                                                    62%                                            Oxidation of Allylic Alcohols to Aldehydes                                    Using DMAP.HCrO.sub.3 Cl                                                      CH.sub.3 CH.sub.2 CH.sub.2 CHCHCH.sub.2 OH                                                         ##STR38##                                                                                ##STR39##                                                                    42%                                             ##STR40##                                                                                         ##STR41##                                                                                ##STR42##                                                                    62%                                              CH.sub.3 (CH.sub.2).sub.5 CHCHCH.sub.2 OH                                                        ##STR43##                                                                                ##STR44##                                                                    90%                                             ##STR45##                                                                                         ##STR46##                                                                                ##STR47##                                                                    72%                                             ##STR48##                                                                                         ##STR49##                                                                                ##STR50##                                                                    88%                                             ##STR51##                                                                                         ##STR52##                                                                                ##STR53##                                                                    55%                                             ##STR54##                                                                                         ##STR55##                                                                                ##STR56##                                                                    75%                                             ##STR57##                                                                                         ##STR58##                                                                                ##STR59##                                                                    74%                                             ##STR60##                                                                                         ##STR61##                                                                                ##STR62##                                                                    26%                                            __________________________________________________________________________

The following examples further illustrate the invention, and it will beunderstood that the invention is not limited thereto.

EXAMPLE 1

This example illustrates the preparation of 4-dimethylaminopyridiniumchlorochromate.

4-Dimethylaminopyridine (4.00 g, 32.8 mmol) is added to an ice-coldvigorously stirred solution of chromium trioxide (3.27 g, 32.7 mmol) in20 ml of 1.65 M aqueous hydrochloric acid resulting in a thickyellow-orange slurry. The slurry is stirred in an ice bath for 30minutes. A yellow-orange solid results which is collected on a sinteredglass funnel, washed with two 10 ml portions of ice cold distilledwater, kept under suction until moderately dry, and placed under vacuumpump pressure until a dry powder forms. The resulting product is4-dimethylaminopyridinium chlorochromate, is obtained in a typical yieldof about 90-92% of the theoretical yield and is analyzed as follows:

C₇ H₁₁ ClCrN₂ O₃ :

Calc %: C, 32.51; H, 4.28; N, 10.82; Cr, 20.11.

Found %: C, 32.70; H, 4.41; N, 10.66; Cr, 20.06.

EXAMPLE 2

This example illustrates the conversion of 3-(4-hydroxymethylphenyl)propanol to its corresponding mono-aldehyde according to the reactionscheme: ##STR63##

3-(4-hydroxymethylphenyl) propanol (0.250 g, 1.5 mmol) is added in oneportion to a stirred suspension of DMAP.HCrO₃ Cl (1.55 g, 6.0 mmol) in25 ml of dichloromethane. The resulting reaction mixture is ayellow-orange suspension. Stirring is continued and the reaction mixtureturns brown-black after about 20 minutes. After the reaction has run forabout 2 hours, the reaction mixture is diluted with 25 ml of ether andfiltered through a lcm Celite® pad. An orange-brown filtrate isrecovered, concentrated to an oil and chromatographed on a 33 mm×20 mmcolumn using silica gel. The resulting product is eluted with chloroformto recover any dialdehyde, and the more polar hydroxyaldehyde is elutedwith ethyl acetate. The desired hydroxyaldehyde is produced in a typicalyield of about 62% whereas the dialdehyde is obtained in a typical yieldof only 2%.

The foregoing Example 2 demonstrates the selectivity of the oxidizingagent of this invention in oxidizing benzylic alcohols to benzylicaldehydes rather than simply oxidizing all alcohol groups of thestarting compound. By way of contrast, when the oxidizing agentpyridinium chlorochromate is employed under normal conditions (1.5 eqchlorochromate, reaction time 20 minutes) to oxidize the diol of Example2, a product is obtained which contains both the mono-aldehyde productin Example 2 and the dialdehyde ##STR64## in yield of about 45% andabout 32% respectively.

EXAMPLE 3

This example illustrates the conversion of an allylic alcohol to analdehyde.

Trans-2-hexenol (0.437 g, 4.3 mmol) in 2 ml dichloromethane is added inone portion to a slurry of DMAP.HCrO₃ Cl in 20 ml dichloromethane whilestirring at room temperature. Stirring is continued for 16 hours duringwhich time dark brown, granular chromium reduction products form. Thereaction mixture is then diluted with about 10 ml of petroleum ether. Adark brown precipitate forms which is removed by vacuum filtrationthrough a 1 cm Celite® pad. The filtrate is recovered and the solventremoved therefrom by distillation via Kugelrohr. The resulting productis trans-2-hexenal which has a boiling point of 50-52° C./20 mm(compared to the boiling point reported in the literature of 49-51°C./20 mm), and is obtained in a typical yield of about 42%.

EXAMPLE 4

This example illustrates the oxidation of the compound ##STR65##

Compound III is added to 4 equivalents of DMAP.HCrO₃ Cl indichloromethane and allowed to react for 6 hours resulting in 44% yieldof the mono-ketone ##STR66## while producing only an 11% yield of theidketone ##STR67##

By way of contrast, when compound III is oxidized with 1.5 equivalentsof pyridinium chlorochromate, approximately equal amounts of IV and Vare produced.

EXAMPLE 5

This example illustrates the oxidation of the compound ##STR68##

Compound VI (0.183 g, 0.59 mmol) is added in one portion to a suspensionof DMAP.HCrO₃ Cl (0.53 g, 2.24 mmol) in 25 ml dichloromethane whilestirring. The resulting reaction mixture is stirred for 4 hours. Brownchromium reduction products form and are removed by vacuum filtrationthrough a l cm Celite® pad. The filtrate is recovered androtary-evaporated to yield a brown oil which is chromatographed on 70 gof alumina to yield, as the major component, the following compound:##STR69## in a typical yield of about 49% while producing less than 3%of the triketone ##STR70##

What I claim and desire to protect by Letters Patent is:
 1. A method ofoxidizing alcohols to their corresponding carbonyl compounds comprisingreacting said alcohol and 4-dimethylaminopyridinium chlorochromate. 2.The method of claim 1 wherein the alcohol is selected from the groupconsisting of allylic and benzylic alcohols.
 3. The method of claim 1wherein the alcohol is a steroid compound.
 4. The method of claim 3wherein the steroid compound has the formula